The multiplication and differentiated behavior of the keratinocyte of stratified squamous epithelia will be examined in detail. Cultures of this cell type contain multiplying and terminally differentiating cells. The control of the transition of the cells from proliferative to terminally differentiating phases will be examined. The principal differentiated products of this cell type are the keratins and the cross-linked envelope. The synthesis of these products is regulated according to the stage of terminal differentiation, which is defined by the position of the cells in the natural epithelium or by the size of the cells. As the cells differentiate they change the keratins they synthesize, and begin the synthesis of new proteins (such as the envelope precursor) not synthesized in the cells of the basal layer. To a considerable extent, these changes also take place in cultured keratinocytes. The control of this process will be studed as a manifestation of controlled gene expression.